HNF4
- Known as:
- HNF4
- Catalog number:
- E021043-2
- Product Quantity:
- 100ug
- Category:
- -
- Supplier:
- EnoGene
- Gene target:
- HNF4
Related genes to: HNF4
- Gene:
- HNF4A NIH gene
- Name:
- hepatocyte nuclear factor 4 alpha
- Previous symbol:
- TCF14, MODY, MODY1
- Synonyms:
- NR2A1, HNF4
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1998-04-20
- Date modifiied:
- 2019-04-23
Related products to: HNF4
Related articles to: HNF4
- Hepatocyte nuclear factor 4α () is a critical transcription factor that regulates the differentiation and metabolism of intestinal epithelial cells. However, its role in piglet growth remains unclear. In this study, the tissue expression of was examined using RT-qPCR, and the putative functional SNPs were analyzed by integrating bioinformatics and DNA sequencing. Association analysis was performed in 156 Min pigs and 160 Landraces, and the biological function of the identified genetic variant was explored using a dual-luciferase reporter assay. The results showed that was widely expressed in liver, kidney and gastrointestinal tissues, with significantly higher expression in the liver of adult pigs than in newborn piglets ( < 0.05). A 20 bp InDel was identified in the first intron of porcine . Allele frequency analysis showed that the Del allele (20 bp deletion) was dominant in Landrace and Duroc pigs, while the In allele (20 bp insertion) was dominant in Min and Jinhua pigs. Association analysis revealed that Min pigs with the In/Del genotype had significantly higher body weights at 14, 21, 28 and 35 days and higher average daily gain (ADG) than those of the In/In animals ( < 0.05). Landrace piglets with the Del/Del genotype exhibited significantly higher body weight at 21 and 28 days than those of the In/Del genotype ( < 0.05). The dual-luciferase reporter assay suggested that the plasmid carrying the In allele exhibited higher transcriptional activity than the Del allele ( < 0.05). Notably, the genotype associated with superior growth performance differed between the two breeds. Collectively, a 20 bp InDel within was identified, which might affect piglet growth partially by modulating its transcription, and further study in other populations with different genetic backgrounds is needed before its application in pig breeding. - Source: PubMed
Publication date: 2026/06/10
Huang JingtongZhang YuZhang YingkunXu RuhaiChen XiaoyuChu XiaohongYang NanaNiu BuyueDai Lihe - The intestinal epithelium is a highly regenerative tissue organized along the crypt-villus axis, where spatially compartmentalized gene expression governs stem cell renewal, proliferation, and differentiation. Super-enhancers (SEs) are large clusters of regulatory elements densely bound by transcription factors (TFs) and cofactors that drive high-level expression of genes controlling cell identity and fate, yet their roles in intestinal epithelial identity and differentiation remain unclear. Here, we generate a spatiotemporal map of SEs in the small intestine, identifying compartment-specific SEs that define crypt and villus programs. Using mouse genetic models, we identify CDX2, HNF4, and SMAD4 as core TFs orchestrating SE-driven transcriptional networks essential for epithelial differentiation. CDX2 is required for SE integrity, and its loss causes widespread SE collapse and silencing of intestinal identity genes. We further demonstrate SE remodeling during colorectal cancer, in which HNF4 and SMAD4 function as SE-associated tumor suppressors that restrain oncogenic enhancer programs. Together, our findings establish SEs as central regulators of intestinal architecture, epithelial fidelity, and tumor progression. - Source: PubMed
Fang WenxinHuang ShuyaXiao RuoxuanWei GuanglingZhang MingyangQiu XiaZou LiVerzi Michael PWang YanChen Lei - Colorectal cancer (CRC) liver metastases are the leading cause of CRC-related mortality, yet the genetic and epigenetic drivers underlying this process remain poorly understood. Here, we established a pro-metastatic CRC organoid library through serial orthotopic transplantation of liver metastasis-derived organoids. Integrative RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses identified a pro-metastatic signature characterized by multilineage plasticity, including fetal-like and basal-like/squamous transcriptional programs. Motif and transcription factor activity analyses identified GATA6 as a key regulator of these epigenetic alterations. GATA6 expression is downregulated in liver metastases, and its genetic ablation enhances liver metastasis with minimal effects on primary tumor growth. Mechanistically, GATA6 loss triggers pro-metastatic transcriptional programs, including fetal-like and basal-like/squamous states, accompanied by LGR5 cell generation. This reprogramming is mediated by the direct repression of HNF4A and increased H3K27ac and occurs independently of SOX17. Together, these findings identify GATA6 loss as a central regulator of multilineage plasticity that drives liver metastasis in CRC. - Source: PubMed
Publication date: 2026/06/22
Goto SaoriDeshpande VikramYilmaz Ömer HGoto Norihiro - Polygenic scores (PGSs) stratify disease risk but often fail to capture individual variation. "Misaligned" individuals, whose observed phenotypes deviate from their genetically expected values based on PGS, provide a powerful model for identifying factors beyond common-variant effects, including additional genetic factors. Here, we apply misalignment classification and enrichment testing frameworks to seven continuous traits and three diseases, assessing whether misaligned individuals in the UK Biobank are enriched for rare (minor-allele frequency [MAF] <0.1%) damaging genetic variation. We identified significant enrichment of predicted loss-of-function (pLoF) variants in COPB2 and GORAB among individuals with lower-than-expected bone mineral density. Regarding stature, shorter-than-expected individuals were enriched for pLoF variants in ACAN and IGF1, while taller-than-expected individuals showed enrichment for damaging missense variants in FBN1. Transitioning from validation to discovery, we performed an exome-wide scan for genes associated with misalignment and identified 74 significant genes, including KANK1, a gene which may have a protective role against primary ovarian insufficiency, and ACSL6, a lipid metabolism gene where damaging missense variation was associated with lower-than-expected BMI. For diseases, results supported a liability threshold model involving counteracting common and rare variant effects. Diagnosed type 2 diabetes mellitus patients with rare pathogenic variants in HNF1A and HNF4A possessed significantly lower polygenic risk than those without. Conversely, coronary artery disease controls harboring protective ANGPTL3 variants had nominally higher polygenic risk. This study highlights the power of misalignment-based analyses in complex continuous phenotypes and disease with the potential to validate known genetic contributors to traits and identify previously unassociated genes. - Source: PubMed
Publication date: 2026/06/22
Baya Nikolas ALassen Frederik HHill BarneyVenkatesh Samvida SCurrant HannahLindgren Cecilia MPalmer Duncan S - Activation of tumor suppressors represents an attractive strategy for cancer treatment. Hepatocyte nuclear factor 4 alpha (HNF4A) functions as a tumor suppressor in the liver by inhibiting hepatocyte proliferation; however, no effective agonists have been identified. Here, we aimed to identify novel ligands for HNF4A and evaluate their role in hepatocarcinogenesis. We identified polyprenoic acid (PA, peretinoin) as the first ligand capable of directly binding HNF4A. Reanalysis of prior clinical trial data revealed that PA suppressed the progression of dysplastic nodules (DNs) to hepatocellular carcinoma (HCC), while showing no effect on local HCC recurrence after initial treatment. Consistently, PA inhibited DN growth but not established HCC in Pdgf-C transgenic mice. Mechanistically, PA selectively bound to the HNF4A P1 isoform, enhancing its transcriptional activity and upregulating hepatocyte maturation markers (ALB, TTR, and SLCO1B3), while suppressing alpha-fetoprotein expression driven by the HNF4A P2 isoform. Importantly, hepatocyte-specific knockdown or lipid-nanoparticle-mediated siRNA abrogated the protective effects of PA. These findings establish HNF4A as a pharmacologically controllable tumor suppressor and highlight PA-like compounds as promising agents for preventing liver carcinogenesis. - Source: PubMed
Publication date: 2026/05/26
Okada HikariNio KoukiOhno NaokiMasuo YusukeHirokawa TakatsuguShimakami TetsuroMiyati TosiakiTakamura HiroyukiOhta TetsuoKitao AzusaKobayashi SatoshiGabata ToshifumiMatsui OsamuKato YukioSeiki MotoharuHonda MasaoKaneko ShuichiYamashita Taro